Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA239580 | ENA |
REPOSITORIES: ENA
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Project description:TG-interacting factor1 (Tgif1) maintains the identity of mouse ES cells by counterbalancing the expression of ES cell core factors
| PRJNA239579 | ENA
Project description:TG-interacting factor1 (Tgif1) is well-known as a transcriptional repressor in transforming growth factor beta (TGFβ) signaling pathway. Target mapping of ES cell core factors in mouse embryonic stem (ES) cells revealed that Tgif1 is occupied by Oct4 and Nanog. Moreover, recent interactome study of mouse gene regulatory regions showed a preferential regulation of Tgif1 by mouse ES cell specific enhancers. However, the detailed role and mode of actions of Tgif1 in stem cell maintenance and development remains elusive. We show that Tgif1 is indispensable for self-renewal and pluripotency of mouse embryonic stem (ES) cells. Aberrant expression of Tgif1 promotes differentiation of ES cells even in the presence of LIF in part by deregulation of pluripotency factors. Intriguingly, we find that Tgif1 level is a critical factor to determine specific lineage commitment in a dosage-dependent manner. We further show that Tgif1 interacts with ES cell core factors and co-localizes at their binding sites, which eventually restricts expression of ES cell core factors including Oct4, Sox2, and Nanog. Taken together, we provide new insights into the roles of Tgif1 in maintenance as well as differentiation of ES cells.
2015-09-26 | GSE55404 | GEO
Project description:TG-interacting factor1 (Tgif1) is well-known as a transcriptional repressor in transforming growth factor beta (TGFβ) signaling pathway. Target mapping of ES core factors in mouse embryonic stem (ES) cells revealed that Tgif1 is occupied by Oct4 and Nanog. Moreover, recent interactome study of mouse gene regulatory regions showed a preferential regulation of Tgif1 by mouse ES cell specific enhancers. However, the detailed role and mode of actions of Tgif1 in stem cell maintenance and development remains elusive. We show that Tgif1 is indispensable for self-renewal and pluripotency of mouse embryonic stem (ES) cells. Aberrant expression of Tgif1 promotes differentiation of ES cells even in the presence of LIF in part by deregulation of pluripotency factors. Intriguingly, we find that Tgif1 level is a critical factor to determine specific lineage commitment in a dosage-dependent manner. We further show that Tgif1 interacts with ES cell core factors and co-localizes at their binding sites, which eventually restricts expression of ES cell core factors including Oct4, Sox2, and Nanog. Taken together, we provide new insights into the roles of Tgif1 in maintenance as well as differentiation of ES cells.
2015-09-26 | GSE55401 | GEO
Project description:Core circuits of transcription factors stabilize stem and progenitor cells by suppressing genes required for differentiation. We do not know how such core circuits are reorganized during cell fate transitions to allow differentiation and lineage choice to proceed. Here, we asked how the pluripotency circuit, a core transcriptional circuit that maintains mouse embryonic stem (ES) cells in a pluripotent state, is dismantled as ES cells differentiate and choose between the neural ectodermal and mesendodermal progenitor cell fates. When ES cells are recultured from pluripotency maintaining conditions to the basal media N2B27, the expression of the pluripotency circuit genes begins to change. At 48 hours post N2B27 addition, the ES cells are competent to respond to differentiation signals. Here, our microarray analysis compares the gene expression profile of ES cells vs. the gene expression profile of cells that have been treated with N2B27 for 48 hours, reaching the competent state. 2 x mouse ES cells in pluripotency maintaining conditions. 3 x mouse ES cells after 48 hr of N2B27 culture
2011-05-03 | E-GEOD-29005 | biostudies-arrayexpress
Project description:Core circuits of transcription factors stabilize stem and progenitor cells by suppressing genes required for differentiation. We do not know how such core circuits are reorganized during cell fate transitions to allow differentiation and lineage choice to proceed. Here, we asked how the pluripotency circuit, a core transcriptional circuit that maintains mouse embryonic stem (ES) cells in a pluripotent state, is dismantled as ES cells differentiate and choose between the neural ectodermal and mesendodermal progenitor cell fates. When ES cells are recultured from pluripotency maintaining conditions to the basal media N2B27, the expression of the pluripotency circuit genes begins to change. At 48 hours post N2B27 addition, the ES cells are competent to respond to differentiation signals. Here, our microarray analysis compares the gene expression profile of ES cells vs. the gene expression profile of cells that have been treated with N2B27 for 48 hours, reaching the competent state.
2011-05-03 | GSE29005 | GEO
Project description:Eric Hesse 9 Jan 2019, 17:34 (15 hours ago) to me, Hartmut Lieber Marcel, unten ist das abstract kopiert, reicht das? Lg, Eric Abstract Osteoporosis is caused by increased bone resorption and decreased bone formation. Intermittent administration of a fragment of Parathyroid hormone (PTH) activates osteoblast-mediated bone formation and is used in patients with severe osteoporosis. However, the mechanisms by which PTH elicits its anabolic effect are not fully elucidated. Here we show that the absence of the homeodomain protein TG-interacting factor 1 (Tgif1) impairs osteoblast differentiation and activity, leading to a reduced bone formation. Deletion of Tgif1 in osteoblasts and osteocytes decreases bone resorption due to an increased secretion of Semaphorin 3E (Sema3E), an osteoclast-inhibiting factor. Tgif1 is a PTH target gene and PTH treatment failed to increase bone formation and bone mass in Tgif1-deficient mice. Thus, our study identifies Tgif1 as a novel regulator of bone remodeling and an essential component of the PTH anabolic action. These insights contribute to a better understanding of bone metabolism and the anabolic function of PTH.
2019-01-29 | PXD012303 | Pride
Project description:Understanding the transcriptional regulatory circuitry responsible for pluripotency and self-renewal in embryonic stem (ES) cells is fundamental to understanding human development and realizing the therapeutic potential of these cells. The transcription factor Oct4 and the chromatin-modifying Polycomb complex, key regulators of ES cell pluripotency and self-renewal, contribute to positive and negative control of a known set of protein-coding genes. MicroRNAs (miRNAs), non-coding transcripts that participate in post-transcriptional gene regulation are also important for normal pluripotency and self-renewal in ES cells, but there has been no systematic investigation of how miRNA expression is controlled by transcriptional regulators of ES cell identity. Here we identify promoters for miRNAs in the human and mouse genomes and describe the subset of these genes that are under the control of Oct4 and Polycomb in ES cells. We find that the majority of miRNAs that are uniquely or preferentially expressed in ES cells are bound by and dependent on Oct4. Oct4 also occupies a set of miRNA genes that are co-occupied by the Polycomb Group protein, Suz12. These miRNAs, repressed in ES cells, are later expressed in differentiated cells in a highly tissue-specific fashion, suggesting that they may contribute to cell-fate determinations. These data reveal how the core transcriptional regulatory circuitry of ES cells controls the miRNA expression program that contributes to pluripotency and self-renewal.
2010-12-01 | E-TABM-365 | biostudies-arrayexpress
Project description:Pluripotent stem cells are defined by their self-renewal capacity, which is the ability of the stem cells to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into any somatic cell lineage. However, understanding the mechanisms that control stem cell fitness versus the pluripotent cell identity is challenging. To investigate the interplay between these two aspects of pluripotency, we performed four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSC self-renewal conditions, and the dissolution of the primed pluripotency identity during early differentiation. Comparative analyses led to the discovery of genes with distinct roles in pluripotency regulation, including mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control pluripotent identity during early differentiation. We further discovered a core set of factors that control both stem cell fitness and pluripotent identity, including a network of chromatin factors that safeguard pluripotency. Our unbiased and systematic screening and comparative analyses disentangle two interconnected aspects of pluripotency, provide rich datasets for exploring pluripotent cell identity versus cell fitness, and offer a valuable model for categorizing gene function in broad biological contexts.
2024-09-05 | PXD055592 | Pride
Project description:c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer, yet functionally differs from the core pluripotency transcription factors, such as Oct4, Sox, and Nanog. Here, we identify a Myc-centered regulatory network in ES cells by combining protein-protein interaction and protein-DNA interaction studies, and show that Myc interacts with the NuA4 histone acetyltransferase complex, previously identified as a critical regulator in ES cell identity. In combination with previously studied transcriptional regulatory network information, we construct three ES cell modules (Core, Polycomb, and Myc) and show that these modules are functionally separable in ES, iPS, MEFs, and partial iPS cells, suggesting that the overall ES cell transcription program is comprised of distinct functional units. With these regulatory modules as an analytical tool, we have reassessed data suggesting that cancer cells reactivate an ES cell-like transcriptional program. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. These observations argue against the hypothesis linking an embryonic gene expression signature with cancer or cancer stem cells. The apparent similarity of cancer and ES cell signatures reflects in large part the pervasive nature of Myc regulatory network. Keywords: Biotin-mediated Chip-chip, Antibody ChIP-chip, Mouse embryonic stem cells
2010-10-14 | GSE20551 | GEO